Based on the previous studies, we hypothesize that after folding of, for example, staphylococcal nuclease the interatomic interactions would be globally coupled to generate extra force for shifting the equilibrium between folding and unfolding in favor of folding and that such coupling would occur on the basis of a line of contacting atoms forming a closed curve in the three- dimensional structure. A result of modulation of this global coupling would be that transformation from one of the conformational energy states to another would involve concerted changes of forces constraining the atomic positions throughout the structure. We have tested this hypothesis using a model system of two isomeric complexes type I and II formed from heme fragment (1-38)H and apoprotein of horse cytochrome c. We investigated 1) kinetics and thermodynamics of interconversion between type I and II forms of complex ferro(1-38)H-(1-104); 2) the CO-binding population; 3) the rate of dissociation of complexes ferri- and ferro(1-38)H-(39-104) (mimicking type II form); and 4) thermal transition of the 695mm absorption band and biological activity. The results indicate a) interconversion between the two forms of complex ferro(1-38)H-(104) occurs without going through dissociation and is associated with enthalpy change favoring type I and entropy change favoring type II; b) the CO-binding population correlates with type II; and c) the redox state of heme appears to influence the thermodynamic relatinship between the two forms. The results suggest that "intra- molecular" flip between ferro-type I and ferro-type II forms would establish the Boltzmann distribution of these two distinctly different energy states, type I form having more strengthened interatomic interactions and type II more pronounced internal motion. Since this model is an exact two-state system by virtue of isomeric complexes, the measured enthalpy and entropy changes can be unambiguously interpreted as relating to changes of internal motion, i.e. changes of forces constraining atomic positions distributed in the structure, revealing new major sources of enthalpy and entropy changes for protein folding.